B2.030 MItochondrial Disease LG

Question 1

what can be seen on a PET scan even prior to cognitive decline in AD patients?

Answer 1

impaired glucose utilization

Question 2

how might reduced mitochondrial function lead to neuronal damage in AD?

Answer 2

reduced cellular energy, leakage of e-, problems with Ca2+ homeostasis, leakage of cyt Q

Question 3

how is PGC1alpha affected in AD?

Answer 3

not activated; reduced activity of mechanisms that promote biogenesis

Question 4

how is mitophagy affected in AD?

Answer 4

defective fusion of autophagosomes and lysosomes

Question 5

what is the net result of changing mitochondrial dynamics in AD?

Answer 5

accumulation of dysfunctional mitochondria
impaired energy production
increased ROS

Question 6

how does mitochondrial dysfunction affect other hallmarks of AD?

Answer 6

increased AB amyloid
-oxidative stress increased gamma secretase activity
increased pTau aggregation driven by impaired Ca2+ homeostasis and oxidative stress

Question 7

how might you stimulate mitophagy/mitobiogenesis to slow or prevent AD?

Answer 7

exercise/caloric restriction

treatment with nicotinamide, precursor to NAD+ that activated PGC1alpha